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Treating amyotrophic lateral sclerosis with allogeneic schwann cell-derived exosomal vesicles: a case report

Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili Patricia Graham Adriana Brooks Risset silvera Alexander J.P.Goldschmidt damien d.Pearse W.dalton dietrich Allan d.Levi James d.Guest Miller school of Medicine University of MiamiMiamiFLUSA stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,schwann cell function may also be ***,important signaling and potential trophic activities of schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FdA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic schwann cell-derived exosomal vesicles to potentially restore impaired schwann cell and motor neuron *** confirmed that cultured schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s schwann cells to allogeneic schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic schwann cell-derived exosomal vesicles diluted in 40 mL of dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction schwann cell

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Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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Neural Regeneration Research 2025年第2期20卷 394-401页

作者： Josep Tomàs Víctor Cilleros-Mañé Laia Just-Borràs Marta Balanyà-segura Aleksandra Polishchuk Laura Nadal Marta Tomàs Carolina silvera-simón Manel M.santafé Maria A.Lanuza Unitat d’Histologia i Neurobiologia(UHNeurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

during the development of the nervous system,there is an overproduction of neurons and *** competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse *** purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this *** particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental *** dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific *** describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon *** downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary ***,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB

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Women in visual neural regeneration research

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Neural Regeneration Research 2025年第2期20卷 489-490页

作者： Tonia s.Rex david J.Calkins Vanderbilt Eye Institute Vanderbilt University Medical CenterNashvilleTNUSA

The year 2024 marks the 60^(th)anniversary of Title IX and 25 years since the New York Times revealed bias against female faculty members at the Massachusetts Institute of *** take an opportunity here to examine the state of gender bias in a relatively new yet already prominent field,neural regeneration in the visual system,for which there is a well-defined context useful for this *** National Eye Institute(NEI)provided the first round of research funding for its Audacious Goals Initiative(AGI)on visual neural regeneration in 2013 and the last round in ***,we focus on this *** sources included PubMed,the National science Foundation(NsF),the NEI,the Blue Ridge Institute for Medical Research and data from the major professional organization for eye and vision research,the Association for Research in Vision and Ophthalmology(ARVO).

关键词： neural visual Times

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Unlocking hypoglycemia–associated brain microvascular dysfunction:critical insights from proteomic analysis

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Neural Regeneration Research 2025年第6期20卷 1707-1708页

作者： siva s.V.P.sakamuri Anil sakamuri department of Chemistry Auburn University at MontgomeryMontgomeryALUSA Vascular Biology Center and department of Medicine Medical College of Georgia at Augusta UniversityAugustaGAUSA

Hypoglycemia-a critical complication linked to worsened brain function in diabetic subjects:Hypoglycemia is characterized by a decline in circulatory glucose levels below sta nda rd physiological *** hypoglycemia,classified as level 1 hypoglycemia,is defined by blood glucose levels below 70 mg/dL and can be effectively addressed through carbohydrate *** hypoglycemia,denoted by blood glucose levels less than 54 mg/dL,poses a life-threatening risk if left *** with type 1 and type 2 diabetes undergoing insulin treatment are particularly susceptible to hypoglycemia due to impaired counterregulatory mechanisms.

关键词： impaired intake critical

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Impact of Zika virus non-structural protein mutations on hippocampal damage

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Neural Regeneration Research 2025年第8期20卷 2307-2308页

作者： Larissa M.G.Cassiano Roney s.Coimbra Neurogenômica/Imunopatologia Instituto RenéRachouFiocruzBelo HorizonteBrazil departamento de Bioquímica e Imunologia Instituto de Ciências BiológicasUniversidade Federal de Minas GeraisBelo HorizonteBrazil

The Zika virus(ZIKV),a member of the Flaviviridae family,attracted worldwide attention for its connection to severe neurological effects,notably microcephaly in newborns,first reported during the 2015 epidemic in ***,its impact goes beyond fetal and neonatal abnormalities,also affecting the central nervous system(CNs)in both children and adults,leading to enduring cognitive and behavioral impairments.

关键词： damage fetal neonatal

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Vagus nerve stimulation in intracerebral hemorrhage:the need for further research

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Neural Regeneration Research 2025年第11期20卷 3213-3214页

作者： sheharyar s.Baig Ali N.Ali Arshad Majid sheffield Institute for Translational Neuroscience Division of NeuroscienceThe University of SheffieldSheffieldUK

Vagus nerve stimulation(VNs)and stroke:stroke is the second leading cause of death and the third leading cause of disability worldwide(Baig et al.,2023).There have been significant paradigm shifts in the management of acute ischemic stroke through mechanical *** chronic ischemic stroke,invasive VNs paired with rehabilitation is associated with a significant increase in upper limb motor recovery and is FdA-approved(Baig et al.,2023).There are no treatments of similar efficacy in acute intracerebral hemorrhage(ICH)where several promising trials,e.g.,TICH-2,sTOP-AUsT,and TRAIGE did not show improvements in functional outcomes(Puy et al.,2023).

关键词： stimulation acute

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Oligodendroglial heterogeneity in health,disease,and recovery:deeper insights into myelin dynamics

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Neural Regeneration Research 2025年第11期20卷 3179-3192页

作者： Pieter-Jan serneels Julie d.de schutter Lies de Groef Lieve Moons steven Bergmans KU Leuven Leuven Brain InstituteDepartment of BiologyAnimal Physiology and Neurobiology DivisionNeural Circuit Development&Regeneration Research GroupLeuvenBelgium KU Leuven Leuven Brain InstituteDepartment of BiologyAnimal Physiology and Neurobiology DivisionCellular Communication&Neurodegeneration Research GroupLeuvenBelgium

decades of research asserted that the oligodendroglial lineage comprises two cell types:oligodendrocyte precursor cells and ***,recent studies employing single-cell RNA sequencing techniques have uncovered novel cell states,prompting a revision of the existing *** forward,the oligodendroglial lineage should be delineated into five distinct cell states:oligodendrocyte precursor cells,committed oligodendrocyte precursor cells,newly formed oligodendrocytes,myelin-forming oligodendrocytes,and mature *** new classification system enables a deeper understanding of the oligodendroglia in both physiological and pathological *** this uniform terminology will facilitate comparison and integration of data across ***,including the consolidation of findings from various demyelinating models,is essential to better understand the pathogenesis of demyelinating ***,comparing injury models across species with varying regenerative capacities can provide insights that may lead to new therapeutic strategies to overcome remyelination ***,by standardizing terminology and synthesizing data from diverse studies across different animal models,we can enhance our understanding of myelin pathology in central nervous system disorders such as multiple sclerosis,Alzheimer's disease,and amyotrophic lateral sclerosis,all of which involve oligodendroglial and myelin dysfunction.

关键词： animal models demyelination fish mammals multiple sclerosis myelin neurodegeneration oligodendrocytes oligodendroglial lineage remyelination

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Nucleoside modified mRNA-lipid nanoparticles as a new delivery platform for the repair of the injured spinal cord

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Neural Regeneration Research 2025年第8期20卷 2311-2312页

作者： Krisztián Pajer Tamás Bellák Antal Nógrádi department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary

spinal cord injury and treatment opportunities:The adult mammalian spinal cord has a very limited capacity for spontaneous regeneration due to various intrinsic molecular and cellular *** the spinal cord neurons have the capacity to regenerate their axons,the expression of growth inhibitory factors,lack or suppression of proper guidance cues,and profound inflammatory responses do not permit successful regeneration(Khyeam et al.,2021).

关键词： injured capacity modified

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Logarithmic Regge pole

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Chinese Physics C 2020年第10期44卷 41-50页

作者： s.d.Campos Applied Mathematics Laboratory-CCTs/dFQM Federal University of Sâo CarlosSorocabaSão Paulo CEP 18052780Brazil

This work presents the subtraction procedure and the Regge cut in the logarithmic Regge pole *** subtraction mechanism leads to the same asymptotic behavior as previously obtained in the non-subtraction *** Regge cut,in contrast,introduces a clear role to the non-leading contributions for the asymptotic behavior of the total *** these results,some simple parameterization is introduced to fit the experimental data for the proton-proton and antiproton-proton total cross-section above some minimum value up to the *** fit parameters obtained are used to present predictions for the ρ(s)-parameter as well as to the elastic slope B(s)at high energies.

关键词： Regge pole double pomeron ρ-parameter total cross section

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An Iterative Relaxation Approach to the solution of the Hamilton-Jacobi-Bellman-Isaacs Equation in Nonlinear Optimal Control

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IEEE/CAA Journal of Automatica sinica 2018年第1期5卷 360-366页

作者： M.d.s.Aliyu department of Electrical Engineering King Faisal University Al-Ahsa 31982 Saudi Arabia IEEE

In this paper, we propose an iterative relaxation method for solving the Hamilton-Jacobi-Bellman-Isaacs equation(HJBIE) arising in deterministic optimal control of affine nonlinear systems. Local convergence of the method is established under fairly mild assumptions, and examples are solved to demonstrate the effectiveness of the method. An extension of the approach to Lyapunov equations is also discussed. The preliminary results presented are promising, and it is hoped that the approach will ultimately develop into an efficient computational tool for solving the HJBIEs.

关键词： Affine nonlinear system bounded continuous function convergence Hamilton-Jacobi-Bellman-Isaacs equation Lyapunov equation relaxation method Riccati equation

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